CD4 mimics targeting the mechanism of HIV entry

Yuko Yamada; Chihiro Ochiai; Kazuhisa Yoshimura; Tomohiro Tanaka; Nami Ohashi; Tetsuo Narumi; Wataru Nomura; Shigeyoshi Harada; Shuzo Matsushita; Hirokazu Tamamura

doi:10.1016/j.bmcl.2009.10.098

CD4 mimics targeting the mechanism of HIV entry

Bioorg Med Chem Lett. 2010 Jan 1;20(1):354-8. doi: 10.1016/j.bmcl.2009.10.098. Epub 2009 Nov 4.

Authors

Yuko Yamada¹, Chihiro Ochiai, Kazuhisa Yoshimura, Tomohiro Tanaka, Nami Ohashi, Tetsuo Narumi, Wataru Nomura, Shigeyoshi Harada, Shuzo Matsushita, Hirokazu Tamamura

Affiliation

¹ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.

PMID: 19926478
DOI: 10.1016/j.bmcl.2009.10.098

Abstract

A structure-activity relationship study was conducted of several CD4 mimicking small molecules which block the interaction between HIV-1 gp120 and CD4. These CD4 mimics induce a conformational change in gp120, exposing its co-receptor-binding site. This induces a highly synergistic interaction in the use in combination with a co-receptor CXCR4 antagonist and reveals a pronounced effect on the dynamic supramolecular mechanism of HIV-1 entry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-HIV Agents / chemical synthesis
Anti-HIV Agents / chemistry*
Anti-HIV Agents / pharmacology
Binding Sites
CD4 Antigens / chemistry*
CD4 Antigens / metabolism
Cell Line
HIV Envelope Protein gp120 / chemistry*
HIV Envelope Protein gp120 / metabolism
HIV Fusion Inhibitors / chemical synthesis
HIV Fusion Inhibitors / chemistry*
HIV Fusion Inhibitors / pharmacology
Humans
Receptors, CXCR4 / antagonists & inhibitors
Receptors, CXCR4 / metabolism
Structure-Activity Relationship

Substances

Anti-HIV Agents
CD4 Antigens
HIV Envelope Protein gp120
HIV Fusion Inhibitors
Receptors, CXCR4